Endocrine Abstracts

Background: Glucocorticoids (GCs) modulate glucose homeostasis by acting on metabolic tissues including liver, adipose and skeletal muscle. GC access to corticosteroid receptors in these tissues is regulated e.g. by pre-receptor metabolism. We recently identified a role for ABCC1, a transmembrane ‘drug-resistance’ transporter, as a GC exporter which limits intracellular GC concentrations and action in adipose tissue. Here, we tested the hypothesis that ABCC1, which i...

A genome wide meta-analysis by the CORtisol NETwork (CORNET) consortium1 has identified genetic variants spanning the SERPINA6/SERPINA1 locus on chromosome 14 associated with changes in morning plasma cortisol and predictive of cardiovascular disease (Crawford et al, Unpublished). SERPINA6 encodes Corticosteroid Binding Globin (CBG) which binds most cortisol in blood and influences delivery of cortisol to target tissues. We hypothesised th...

Background: Adipose tissue dysfunction could partially explain the well-demonstrated association between obesity and survival in breast cancer (BC). Oestrogen and glucocorticoid concentrations and their respective activation enzymes, oestrogenic 17β-hydroxysteroid dehydrogenases (17βHSDs) and aromatase, and 11βHSD1 are increased in adipocyte hyperplasia and hypertrophy, supporting the hypothesis of a potential role for locally generated steroids in obesity-assoc...

Background: The CRISPR/Cas9 genome-editing platform is a powerful technology to create genetically engineered cells and organisms. However, the success of CRISPR genome editing experiments is limited by the intracellular delivery and expression of Cas9 endonuclease protein and guide RNA (gRNA). Beta-tumour cells (βTC-6), derived from transgenic mice, exhibit glucose stimulated insulin secretion which makes them a valuable tool in understanding the mechanisms that regulate...

Background: Congenital Hyperinsulinism (CHI) is characterized by the unregulated secretion of insulin in the presence of hypoglycaemia. The mutations in ABCC8 and KCNJ11, which encode the sulfonylurea receptor 1 (SUR1) and potassium inward-rectifying 6.2 (Kir6.2) subunits of ATP-sensitive potassium channel (K channel), are the most common identified cause of the condition. Defects in the HADH gene are responsible for SCHAD-HI, a rare form of the disease caused by the disruptio...

Introduction: The placenta interchanges nutrients, oxygen and waste between mother and fetus, acts as a gate-keeper to protect the fetus and creates an optimal endocrine environment to maintain the pregnancy. Placental insufficiency underpins common pregnancy complications (e.g. intrauterine growth restriction, preterm birth). Perturbed expression of molecular transporter proteins in the placental syncytiotrophoblast will affect fetal exposure to harmful drugs/xenobiotics such...

Intracellular cortisol is regulated by 11βHSD1. Although the field has focused on regeneration of cortisol from inert cortisone by 11β-reductase activity of 11βHSD1, we have used stable isotope tracers and arteriovenous sampling to quantify simultaneous dehydrogenase (cortisone generation) and reductase (cortisol regeneration) in human adipose and skeletal muscle. In vitro studies suggest insulin regulates this balance of reductase vs dehydrogenase acti...

Background: Chromosome analysis is always indicated in disorders of sex development (DSD), but the need for karyotyping in gender dysphoria (GD) is less clear.Aims and objectives: We therefore aimed to review the place of routine chromosome analysis in the management of GD in children and adolescents.Patients and methods: Five hundred and twenty children and adolescents with GD have been referred at the time of reporting to the two...

Congenital adrenal hyperplasia (CAH) is associated with poor health outcomes. This is, in part, because doses of glucocorticoid sufficient to suppress excess adrenal androgens are also associated with adverse metabolic effects such as insulin resistance. This toxicity occurs with efficacious doses of all commonly prescribed glucocorticoids (hydrocortisone, prednisolone and dexamethasone). However, the glucocorticoid corticosterone may have an improved therapeutic index because...

Background: The 5α-reduced glucocorticoid, 5α-tetrahydrocorticosterone (5α-THB), displays a dissociated steroid profile exhibiting anti-inflammatory effects in a murine model of thioglycollate-induced peritonitis but failing to induce adverse metabolic effects caused by corticosterone. We assessed the topical anti-inflammatory properties of 5α-THB in a model of irritant dermatitis. Given the adverse effects of steroids on cutaneous wound healing, we also in...